Knox's appeal is focused on the evidence in the case, or rather the lack of it. Her team has argued that the DNA evidence is sketchy, and that despite the bloody crime scene found around Kercher, Amanda Knox's DNA was not found at the scene. Some of Knox's DNA was found on a knife believed to be the murder weapon, but since Knox and the victim were roommates, it's possible that the DNA got on the knife by completely innocent methods.

The defense has also argued that investigators botched the case by tainting the DNA evidence.